Resorbable barrier micro-membranes for attenuation of scar tissue during healing

ABSTRACT

Resorbable polylactide polymer scar tissue reduction barrier membranes and methods of their application are disclosed. The scar-tissue reduction barrier membranes are constructed entirely of polylactide resorbable polymers, which are engineered to be absorbed into the body relatively slowly over time in order to reduce potential negative side effects. The scar tissue reduction barrier membranes are formed to have thicknesses on the order of microns, such as, for example, thicknesses between 10 and 300 microns. The membranes are preshaped with welding flanges and stored in sterile packaging.

RELATED APPLICATIONS

This application is a continuation of Ser. No. 09/805,411 filed Mar. 12,2001 now U.S. Pat. No. 6,531,146, which claims the benefit of priorityunder 35 U.S.C. section 119(e) of provisional application No.60/231,800, filed Sep. 11, 2000, and of provisional application No.60/196,869, filed Mar. 10, 2000.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and, moreparticularly, to devices and methods for attenuating the formation ofpost-surgical adhesions between a post-surgical site and adjacentsurrounding tissue.

BACKGROUND OF THE INVENTION

A major clinical problem relating to surgical repair or inflammatorydisease is adhesion which can occur during the initial phases of thehealing process after surgery or disease. Adhesion is a condition whichinvolves the formation of abnormal tissue linkages. These linkages canfor example impair bodily function, produce infertility, obstruct theintestines and other portions of the gastrointestinal tract (bowelobstruction) and produce general discomfort, e.g. pelvic pain. Thecondition can in some instances be life threatening. The most commonform of adhesion occurs after surgery as a result of surgicalinterventions, although adhesion may occur as a result of otherprocesses or events such as pelvic inflammatory disease, mechanicalinjury, radiation treatment and the presence of foreign material.

Various attempts have been made to prevent postoperative adhesions. Forexample, the use of peritoneal lavage, heparinized solutions,procoagulants, modification of surgical techniques such as the use ofmicroscopic or laparoscopic surgical techniques, the elimination of talcfrom surgical gloves, the use of smaller sutures and the use of physicalbarriers (membranes, gels or solutions) aiming to minimize apposition ofserosal surfaces, have all been attempted. Unfortunately, limitedsuccess has been seen with these methods. Barrier materials, in variousforms such as membranes and viscous intraperitoneal solutions, which aredesigned to limit tissue apposition, have also met with only limitedsuccess. A few of these barrier materials include cellulosic barriers,polytetrafluoroethylene materials, and dextran solutions.

U.S. Pat. No. 5,795,584 to Tokahura et al. discloses anti-adhesion orscar tissue reduction films or membranes, and U.S. Pat. No. 6,136,333 toCohn et al. discloses similar structures. In the Tokahura et al. patent,a bioabsorbable polymer is copolymerized with a suitable carbonate andthen formed into a non-porous single layer adhesion barrier, such as afilm. In the Cohn et al. patent, a polymeric hydrogel for anti-adhesionis formed without crosslinking by using urethane chemistry. Both ofthese patents involve relatively complex chemical formulas and/orreactions to result in particular structures to be used as surgicaladhesion barriers.

SUMMARY OF THE INVENTION

Resorbable polylactide polymer scar tissue reduction barrier membranesand methods of their application have been discovered. In accordancewith one aspect of the present invention, the scar-tissue reductionbarrier membranes are constructed entirely of polylactide resorbablepolymers, which are engineered to be absorbed into the body relativelyslowly over time in order to reduce potential negative side effects. Thescar tissue reduction barrier membranes are formed to have thicknesseson the order of microns, such as, for example, thicknesses between 10and 300 microns. The membranes are preshaped with welding flanges andstored in sterile packaging.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a laminotomy procedure wherein a portion of theposterior arch (lamina) of a vertebra is surgically removed;

FIG. 2 is an enlarged view of FIG. 2;

FIG. 3 illustrates a scar-reduction resorbable barrier micro-membranefor application to the exiting nerve root of the spinal chord inaccordance with a first pre-formed embodiment of the present invention;

FIG. 4 illustrates a scar-reduction resorbable barrier micro-membranefor application to two exiting nerve roots of the spinal chord inaccordance with a second pre-formed embodiment of the present invention;

FIG. 5 illustrates a scar-reduction resorbable barrier micro-membranefor application to four exiting nerve roots of the spinal chord inaccordance with a third pre-formed embodiment of the present invention;

FIG. 6a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a fourth pre-formed embodiment of thepresent invention;

FIG. 6b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 6a;

FIG. 7a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a fifth pre-formed embodiment of the presentinvention;

FIG. 7b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 7a;

FIG. 8a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a sixth pre-formed embodiment of the presentinvention;

FIG. 8b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 8a;

FIG. 9a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a seventh pre-formed embodiment of thepresent invention;

FIG. 9b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 9a;

FIG. 10a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with an eighth pre-formed embodiment of thepresent invention;

FIG. 10b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 10a;

FIG. 11a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a ninth pre-formed embodiment of the presentinvention;

FIG. 11b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 11a;

FIG. 12a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a tenth pre-formed embodiment of the presentinvention;

FIG. 12b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 12a;

FIG. 13a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with an eleventh pre-formed embodiment of thepresent invention;

FIG. 13b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 13a;

FIG. 14a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a twelfth pre-formed embodiment of thepresent invention;

FIG. 14b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 14a;

FIG. 15a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a thirteenth pre-formed embodiment of thepresent invention;

FIG. 15b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 15a;

FIG. 16a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a fourteenth pre-formed embodiment of thepresent invention;

FIG. 16b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 16a;

FIG. 17a is a top planar view of a scar-reduction resorbable barriermembrane in accordance with a fifteenth pre-formed embodiment of thepresent invention; and

FIG. 17b is a cross-sectional view of the scar-reduction resorbablebarrier membrane shown in FIG. 17a.

FIG. 18 is illustrates a scar-reduction resorbable barriermicro-membrane of the present invention implanted on a rat spine, withtwo spinus processes of the spine protruding at opposing ends of theimplant;

FIG. 19 is a bar graph showing the results of a study comparing thescar-reduction barrier membrane of the present invention against severalother materials, and controls, indicating the percent collagen found inand around the dura following a surgical procedure after a period ofabout three weeks;

DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

The present invention provides a resorbable implant in membrane formthat can be used in various surgical contexts to retard or preventtissue adhesions, and reduce scarring. The polylactide polymers andco-polymers of the present invention require relatively simple chemicalreactions and formulations. It is believed that the presentscar-reduction resorbable barrier membranes of polylactide polymers andco-polymers can induce relatively minor localized tissue inflammation,but that inflammation is believed to be minimized as a result of thepresently engineered compositions, constructions, and applications asset forth herein, to thereby yield highly effective scar tissuereduction.

The scar-reduction resorbable barrier membrane of the present inventionmay be more effective than other membranes because it is very smooth andnon-porous. Moreover, the barrier membrane is preferably bioabsorbablein the body. The lack of porosity acts to form a barrier that does notallow interaction of the tissues. The non-porosity and the smoothness ofthe barrier membrane can reduce tissue turbulence, enhance tissueguidance, and minimize scar formation. Moreover, the smooth,uninterrupted surface of the barrier membrane material may facilitatemovement of the dura and local tissues across the area, hence reducingfrictional rubbing and wearing which may induce scar tissue formation.

As used herein, the term “non-porous” refers to a material which isgenerally water tight and, in accordance with a preferred embodiment,not fluid permeable. However, in a modified embodiment of the inventionmicro-pores (i.e., fluid permeable but not cell permeable) may exist inthe scar-reduction resorbable barrier membrane of the present invention,to the extent, for example, that they do not substantially disrupt thesmoothness of the surfaces of the resorbable barrier membrane to causescarring of tissue. In substantially modified embodiments for limitedapplications, pores which are cell permeable but not vessel permeablemay be manufactured and used. As presently preferred, the resorbablebarrier membrane is manufactured using a press molding procedure toyield a substantially non-porous film. The barrier membrane materials ofpresent invention may have a semi-rigid construction, and are fullycontourable when heated to approximately 55 degrees Celsius. Aspresently embodied, many of the thinner membrane thicknesses can besufficiently contoured even in the absence of heating.

The material can be used in a number of surgical applications,including: surgical repair of fracture orbital floors, surgical repairof the nasal septum and perforated ear drum barrier membrane, as aprotective sheathing to facilitate osteogenesis, surgical repair of theurethral anatomy and repair of urethral strictures, prevention ofsynostosis in completed corrective surgery for cranial fusions andforearm fractures, lessening of soft-tissue fibrosis or bony growth, asa temporary covering for prenatal rupture omphalocele during stagedrepair procedures, guided tissue regeneration between the teeth andgingival margin, tympanic membrane repairs, dural coverings and neuralrepair, heart vessel repair, hernia repair, tendon anastomoses,temporary joint spacers, wound dressings, scar coverings, and as acovering for gastroschisis. The barrier membrane material of the presentinvention is particularly suitable for preventing tissue from abnormallyfibrotically joining together following surgery, which can lead toabnormal scarring and interfere with normal physiological functioning.In some cases, such scarring can force and/or interfere with follow-up,corrective, or other surgical operations. For example, there is evidencepointing to epidural adhesions as possible factors contributing tofailed back surgery. Epidural fibrosis may occur following spinalinjuries or as a post-operative surgical complication. The dense scarformation on dura and around nerve roots has previously been describedas the “laminotomy membrane,” and has been implicated in renderingsubsequent spine operations technically more difficult. In alamininectomy procedure, for example, the scar-reduction resorbablebarrier membrane of the present invention is desirably inserted betweenthe dural sleeve and the paravertebral musculature post laminotomy andconforms readily to block exposed marrow elements of the laminae.Imposition of the membrane material as a barrier between theparavertebral musculature and the epidural space is believed to reducecellular trafficking and vascular invasion into the epidural space fromthe overlying muscle and adjacent exposed cancellous bone. Moreover,tests have shown that the present barrier membrane material does notappear to interfere with normal posterior wound healing while at thesame time inhibiting the unwanted adhesions and scarring.

In a preferred embodiment of the present invention, the barrier membranematerial comprises a poly lactide polymer or co-polymer and, morepreferably, comprises poly (L-lactide-co-D,L-lactide) 70:30 ResomerLR708 manufactured and supplied from Boehringer Ingelheim KG of Germany.A pre-formed membrane made from the material can be shaped at the timeof surgery by bringing the material to its glass transition temperature,using heating iron, hot air, heated sponge or hot water bath methods.The scar-tissue reduction barrier membrane of the present inventionpreferably has a uniform thickness of less than about 300 microns,preferably less than 200 microns, and more preferably between 10 micronsand 100 microns. As defined herein, the “micro-membranes” of the presentinvention comprise thicknesses between 10 microns and 300 microns and,preferably, between 10 and 100 microns.

The very thin construction of these micro-membranes is believed tosubstantially accelerate the rate of absorption of the implants,compared to rates of absorption of thicker membrane implants of the samematerial. It is believed, however, that resorption into the body tooquickly of the micro-membrane will yield undesirable drops in local pHlevels, thus introducing/elevating, for example, local inflammation,discomfort and/or foreign antibody responses. Further, a resultinguneven (e.g., cracked, broken, roughened or flaked) surface of a barriermembrane degrading too early may undesirably cause tissue turbulencebetween the tissues before, for example, adequate healing has occurred,resulting in potential tissue inflammation and scarring. It is believedthat a micro-membrane of the present invention having a thickness ofabout 200 microns or less should maintain its structural integrity for aperiod in excess of three weeks and, more preferably for at least 7weeks, before substantially degrading, so that the anti-scarringfunction can be achieved and optimized. To the extent the micro-membranedoes not degrade at an accelerated rate, compared to a thicker membraneof the same material, the membrane should maintain its structuralintegrity for a period in excess of 6 months and, more preferably for atleast one year, before substantially degrading, in order to achieve andoptimize the anti-scarring function. The polylactide resorbable polymerbarrier membranes in accordance with this aspect of the presentinvention are thus designed to resorb into the body at a relatively slowrate.

The object of reducing acidity levels and/or tissue turbulence, and anyaccompanying inflammation (e.g., swelling), at the post-surgical site isbelieved to be of particular importance in the context of spinalsurgeries, which are often performed for the very purpose of relievinginflammation-induced discomfort. It is believed that nerve tissue can beparticularly sensitive to, for example, slightly elevated acidity levelsand inflammation. During a typical spinal surgical procedure, such as,for example, a laminotomy, a portion of the lamina structure is removedfrom a patient's vertebrae in order to, for example, provide access tothe spinal column and/or disk.

The barrier membrane material may be provided in rectangular membranesthat are for example several centimeters on each side, or can be cut andformed into specific shapes, configurations and sizes by themanufacturer before packaging and sterilization. In modifiedembodiments, various known formulations and copolymers of poly lactidesmay affect the physical properties of the scar-reduction resorbablebarrier membrane and/or the bridging membrane. The thin barriermembranes of the present invention are sufficiently flexible to conformaround anatomical structures, although some heating in a hot water bathmay be necessary for thicker configurations. In modified embodiments,certain poly lactides which become somewhat more rigid and brittle atthicknesses above 0.25 mm and which can be softened by formation with acopolymer and another polylactide, for example, may be implemented toform scar-reduction resorbable barrier micro-membrane. Moreover, inaccordance with another aspect of the present invention, the scar-tissuereduction barrier micro-membrane and/or the bridging membrane, (definedinfra) may comprises a substance for cellular control, such as at leastone of a chemotactic substance for influencing cell-migration, aninhibitory substance for influencing cell-migration, a mitogenic growthfactor for influencing cell proliferation, a growth factor forinfluencing cell differentiation, and factors which promoteneoangiogenesis (formation of new blood vessels).

Referring more particularly to the drawings, FIG. 1 illustrates alaminotomy procedure wherein a the two vertebrae 20 and 22 are separatedand fixated using screws 24 and rods 26, and a portion of the lamina hasbeen removed, leaving a window 28 (shown as a phantom rectangle) in thevertebrae 22. FIG. 2 is an enlarged view of the window 28 in the laminaof the vertebrae 22. The spinal chord 30 and an exiting nerve root 32are thus exposed. In accordance with the present invention, thescar-reduction resorbable barrier micro-membrane is applied to the duraof both the spinal chord 30 and the exiting nerve root 32, to therebyattenuate or eliminate the occurrence of post-operative scarring in thevicinity of the exiting nerve root 32. In a modified embodiment, athicker bridging membrane is applied to one or both of the vertebrae 20and 22, to thereby bridge (i.e., tent) over and cover the window 28.This bridging membrane may be non-porous, fluid permeable, cellpermeable or vessel permeable in accordance with various embodiments,and preferably comprises a thickness between about 0.5 mm and 2.0 mm forpreventing prolapse of adjacent muscle tissue into the foramen (i.e.,the spinal lumen containing the spinal chord 30 and exiting nerve root32). In accordance with various embodiments, the bridging membrane maybe used alone or in combination with the scar-reduction resorbablebarrier micro-membrane or, the scar-reduction resorbable barriermembrane may be used without the bridging membrane.

Various means for attaching the barrier membrane to structures such asmuscular tissue, other soft tissue, or bone are contemplated. Forexample, sutures or staples may be used to attach the membrane to theparavertebral muscle. As another example, the bridging membrane inparticular may be secured to the vertebrae bone using resorbable bonescrews or tacks. Tucking or folding the membrane material intoanatomical crevices may be sufficient to fix its position. An adhesivesuch as a fibrin sealant, or a resorbable cyanoacrylate adhesive mayfurther be utilized to secure the membranes, alone or in combinationwith the above means of attachment.

In accordance with one aspect of the present invention, thescar-reduction resorbable barrier micro-membrane can be heat bonded,such as with a bipolar electro-cautery device, ultrasonicly welded, orsimilarly sealed directly to the dura of the spinal chord 30 and theexiting nerve root 32. Such a device can be used to heat the barriermembrane at various locations, such as at the edges and at points in themiddle, at least above its glass transition temperature, and preferablyabove its softening point temperature. The glass transition temperatureof the preferred material is about 55° Celsius, while its softeningpoint temperature is above 110° Celsius. The material is heated alongwith adjacent tissue such that the two components bond together at theirinterface. In another embodiment, the scar-reduction resorbable barriermembrane can be heat bonded or sealed directly to one or both of thevertebrae 20 and 22, or to muscle or other soft tissue, for example. Inyet another embodiment, the scar-reduction resorbable barriermicro-membrane can be heat bonded or sealed directly to itself in anapplication, for example, wherein the micro-membrane is wrapped around astructure and then heat joined to itself. Moreover, the technique ofheat-sealing the barrier membrane material to itself or body tissue maybe combined with another attachment method for enhanced anchoring. Forexample, the barrier membrane material may be temporarily affixed inposition using two or more points of heat sealing (i.e., heat welding)using an electro-cautery device, and sutures, staples or glue can thenbe added to secure the barrier membrane into place.

Turning to FIG. 3, a pre-formed scar-reduction resorbable barriermicro-membrane 34 is formed with a first welding flange 36 and a secondwelding flange 38 thereon. A trunk portion 40 fits over the spinal chord30, and a branch portion 42 fits over the exiting nerve root 32. Thefirst welding flange 36 is formed by a first slit 44 and a second slit46, and the second welding flange 38 is formed by a first slit 48 and asecond slit 50. In application, the pre-formed scar-reduction resorbablebarrier micro-membrane 34 is placed over the spinal chord 30 and theexiting nerve root 32 and, subsequently, the first welding flange 36 andthe second welding flange 38 are bent at least partially around theexiting nerve root. The rounded end 52 of the branch portion 42 fitsonto a portion of the exiting nerve root 32 furthest away from thespinal chord 30. As presently embodied, the first welding flange 36 andthe second welding flange are wrapped around, and preferably tuckedbeneath (i.e., behind) the exiting nerve root 32. In a preferredembodiment, the first welding flange 36 is then heat welded to thesecond welding flange 38. The flanges preferably are cut to wrapentirely around the exiting nerve root 32 and overlap one another. Thefirst welding flange 36 may be sutured to the second welding flange 38,alone or in addition with the heat welding step, to thereby secure thefirst welding flange 36 to the second welding flange 38. In anotherembodiment, neither heat welding nor suturing are used and the flangesare merely tucked partially or completely around the exiting nerve root32 (depending on the dimensions of the root 32). When sutures are to beused, the pre-formed scar-reduction resorbable barrier micro-membrane 34may be pre-formed and packaged with optional suture apertures 60. Theedges 64 and 66 are then preferably heat welded to the spinal chord 30.The two edges 68 and 70 form a third welding flange 72. A fourth weldingflange 74 is formed by slits 76 and 78, and a fifth welding flange 80 isformed by slits 82 and 84. The welding flanges may be secured in mannerssimilar to those discussed in connection with the welding flanges 36 and38. Heat welds may further be secured along other edges and along thesurface of the pre-formed scar-reduction resorbable barriermicro-membrane 34, such as shown at 90 in FIG. 18. Moreover, notches maybe formed on the membranes of the present invention, such as, forexample, at the ends 64 and 66 in modified-shape embodiments, foraccommodating, for example, the spinal processes. Such exemplary notchesare shown in FIG. 18 at 92.

FIG. 4 illustrates a scar-reduction resorbable barrier micro-membranefor application to two exiting nerve roots 32 and 98 of the spinal chordin accordance with another pre-formed embodiment of the presentinvention. FIG. 5 illustrates a scar-reduction resorbable barriermicro-membrane similar to that of FIG. 4 but adapted for application tofour exiting nerve roots of the spinal chord in accordance with anotherpre-formed embodiment of the present invention. For example, the branchportion 100 is analogous in structure and operation to the branchportion 42 of the FIG. 3 embodiment, and the other branch portion 102 isconstructed to accommodate the exiting nerve root 98. Simlar elementsare shown in FIG. 5 at 100 a, 102 a, 100 b and 102 c. The embodiments ofFIGS. 6-17 illustrate other configurations for accommodating differentanatomical structures. For example, the configurations of FIGS. 7, 10,12, 14 and 15 are designed to be formed into, for example, a conestructure to fit around a base portion with a protrusion extendingthrough the center of the membrane. The illustrated embodiments of FIGS.6-17 have suture perforations formed around their perimeters, and manyare shown with cell and vessel permeable pores.

In accordance with the present invention, the pre-formed scar-reductionresorbable barrier micro-membranes are preformed and sealed insterilized packages for subsequent use by the surgeon. Since anobjective of the scar-reduction resorbable barrier micro-membranes ofthe present invention is to reduce sharp edges and surfaces,preformation of the membranes is believed to help facilitate, albeit toa relatively small degree, rounding of the edges for less rubbing,tissue turbulence and inflammation. That is, the surfaces and any sharpedges of the scar-reduction resorbable barrier micro-membranes arebelieved to be capable of slightly degrading over time in response toexposure of the membranes to moisture in the air, to thereby formrounder edges. This is believed to be an extremely minor effect.Moreover, sterilization processes (E-beam or heat) on the cut,pre-packaged and/or packaged membrane can further round any sharp edges,as can any initial heating to glass temperature of the pre-cut membranesjust before implanting. Moreover, the very thin scar-reductionresorbable barrier micro-membranes of the present invention may beparticularly susceptible to these phenomena, and, perhaps to a morenoticeable extent, are susceptible to tearing or damage from handling,thus rendering the pre-forming of the scar-reduction resorbable barriermicro-membranes beneficial for preserving the integrity thereof.

An embodiment of the scar-reduction resorbable barrier membrane has beentested in rat studies in comparison with several scar-tissue reductionbarrier gels with favorable results. Specifically, the barrier membranematerial of the present invention and the scar-tissue reduction gelswere inserted around the spinal column of 52 male adult Sprague-Dawleyrats, each weighing 400 plus grams. A posterior midline incision wasmade exposing the bony posterior elements from L4 to L7, and bilaterallaminectomies were performed at the L5 and L6 level using surgicalloupes. Following the laminectomies, the dura was retracted medially (tothe left then to the right) using a microscope to expose the disc atL5/L6, and a bilateral controlled disc injury was performed using a 26gauge needle. After hemostasis and irrigation, an anti-inflammatoryagent was applied over both laminectomy sites.

The rats were divided and treated in five groups: 1) normal controlswithout surgery; 2) untreated, laminectomy only; 3) those to which 0.1cc of high molecular weight hyaleronan (HA gel) was applied to thelaminectomy site; 4) those to which 0.1 cc of Adcon-L scar-tissuereduction gel was applied to the laminectomy site; and 5) those that hadan insertion of a barrier membrane of the present invention over thelaminectomy site. The wounds were closed in a routine manner, and thesurvival period was three weeks.

After termination of each of the rats, the L5 segmental nerve roots weredissected free bilaterally using an anterior approach. The segmentalnerve roots were excised including the portion of the nerve root withinthe foramen (1 cm in length). Additionally, the dura was exposed usingan anterior approach. The dura from the caudal aspect of the body of L4to the cephalad aspect of the body of L7 was removed (1.5 center inlength) including all attached scar. The samples were analyzedbiochemical by extracting the fat, then vacuum drying and determiningthe amount of total collagen and the percent of collagen from thehydroxyproline content. The amount of total collagen was expressed inmilligrams and the percent of collagen was expressed as a percent of fatfree dry weight.

Each treatment group was compared to both the normal controls and theoperated but untreated controls using a Fisher's multiple comparisonspaired t-test. Additionally, the treatment groups were compared using aone-way analysis of variance. In the untreated, laminotomy-onlyspecimens, the total collagen increased more than two-fold in the dura(p value of 0.0009). In the untreated group, the percent collagenincreased significantly in both the dura and nerve roots (p values of0.001 and 0.005, respectively). Treatment with HA gel (p=0.010), Adcon-L(p=0.004), or the barrier membrane of the present invention (p=0.002)significantly reduced the amount of total collagen in the dura.Likewise, the same holds true for the percent collagen where the valuesare: HA gel (p=0.015), Adcon-L (p=0.041), and the barrier membrane ofthe present invention (p=0.011). There was a trend showing that thebarrier membrane of the present invention decreased approximately 50%more both in total collagen and percent collagen compared to the HA geland Adcon-L. In the nerve roots, the amount of total collagen and apercentage of collagen was not significantly changed by treatment withany of the HA gel, Adcon-L, or barrier membrane of the presentinvention.

These biochemical measurements of total and percent collagen enabledobtension of quantitative data on scar formation post laminotomy. Grossfindings and biochemical analysis in the model demonstrated that theuntreated laminotomy scar becomes adherent to the dorsum of the duramater, a clearly undesirable outcome. Both a single application of HAgel or Adcon-L demonstrated a beneficial effect at the level of thedura. However, the half life of HA gel is less than 24 hours, and theAdcon-L is resorbed within approximately four weeks, which suggests thatfurther long-term studies could be conducted. Additionally, Adcon-L hasthe potential to delay posterior wound healing, possibly leading towound infections and/or wound dehiscences (few of the adverse eventsexperienced by less than 1% of the study groups per product pamphlet).On the other hand, the barrier membrane of the present invention appearsto wall off the overlying muscle, potentially protecting againstcellular trafficking and vascular ingrowth, and does not appear tointerfere with normal posterior wound healing. A possible improvement onthe results obtained by using the barrier membrane of the presentinvention by itself may be obtained by using the barrier membrane inconjunction with an anti-inflammatory gel agent applied, for example,beneath the barrier membrane. Additionally, the scar-tissue reductionbarrier membrane may be used in combination with a fixation device forstabilizing the bone defect, such as shown in connection with the twovertebrae 20 and 22 of FIG. 1.

FIG. 19 illustrates a bar graph showing the percent collagen resultingfrom the aforementioned rat tests for various groups. The results forthe barrier membrane of the present invention are labeled as Macropore,while the last result denoted MAC+HA is for the membrane material of thepresent mention in conjunction with HA gel. The results indicate thatthere is a marked improvement over the HA gel or Adcon-L, andsignificant improvement in comparison with a tissue growth factor betaand a material known as Decorin.

While the foregoing is a complete description of the preferredembodiments of the invention, various alternatives, modifications, andequivalents may be used. Moreover, it will be obvious that certain othermodifications may be practiced within the scope of the appended claims.

What is claimed is:
 1. A resorbable scar-tissue reduction micro-membrane for attenuating a formation of post-surgical scar tissue between a healing post-surgical site and adjacent surrounding tissue following an in vivo surgical procedure on the post-surgical site, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant is formed between the post-surgical site and the adjacent surrounding tissue, the implant comprising. a substantially planar membrane of resorbable polymer base material having a first substantially-smooth side and a second substantially-smooth side, the substantially planar membrane of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first substantially-smooth side and the second substantially-smooth side, the single layer of resorbable polymer base material having a substantially uniform composition; wherein a thickness of the single layer of resorbable polymer base material, measured between the first substantially-smooth side and the second substantially-smooth side, is between about 10 microns and about 300 microns; wherein the single layer of resorbable polymer base material is non-porous; and wherein the single layer of resorbable polymer base material is adapted to maintain a smooth-surfaced barrier between the healing post-surgical site and the adjacent surrounding tissue for a relatively extended period of time sufficient to attenuate or eliminate any formation of scar tissue between the post-surgical site and the adjacent surrounding tissue, and is adapted to be resorbed into the mammalian body within a period of approximately 18 to 24 months from an initial implantation of the implant into the mammalian body.
 2. The resorbable scar-tissue reduction micro-membrane as set forth in claim 1, wherein the resorbable polymer base material is 70:30 poly (L-lactide-co-D,L-lactide).
 3. The resorbable scar-tissue reduction micro-membrane as set forth in claim 1, wherein the resorbable polymer base material is poly-L-lactide.
 4. The resorbable scar-tissue reduction micro-membrane set forth in claim 1, wherein the thickness is about 100 microns.
 5. The resorbable scar-tissue reduction micro-membrane as set forth in claim 1, wherein the thickness is about 200 microns.
 6. The resorbable scar-tissue reduction micro-membrane as set forth in claim 1, wherein the single layer of resorbable polymer base material is not fluid permeable.
 7. The resorbable scar-tissue reduction micro-membrane as set forth in claim 1, wherein the resorbable scar-tissue reduction micro-membrane is impregnated with at least one of a chemotactic substance for influencing cell-migration, an inhibitory substance for influencing cell-migration, a mitogenic growth factor for influencing cell proliferation and a growth factor for influencing cell differentiation.
 8. The resorbable scar-tissue reduction micro-membrane set forth in claim 1, wherein the resorbable scar-tissue reduction micro-membrane is sealed in a sterile packaging.
 9. The resorbable scar-tissue reduction micro-membrane set forth in claim 2, wherein the thickness is about 100 microns.
 10. The resorbable scar-tissue reduction micro-membrane as set forth in claim 2, wherein the thickness is about 200 microns.
 11. The resorbable scar-tissue reduction micro-membrane as set forth in claim 2, wherein the single layer of resorbable polymer base material is not fluid permeable.
 12. The resorbable scar-tissue reduction micro-membrane as set forth in claim 2, wherein the resorbable scar-tissue reduction micro-membrane is impregnated with at least one of a chemotactic substance for influencing cell-migration, an inhibitory substance for influencing cell-migration, a mitogenic growth factor for influencing cell proliferation and a growth factor for influencing cell differentiation.
 13. The resorbable scar-tissue reduction micro-membrane set forth in claim 2, wherein the resorbable scar-tissue reduction micro-membrane is sealed in a sterile packaging.
 14. A resorbable scar-tissue reduction membrane for attenuating a formation of post-surgical scar tissue between a healing post-surgical site and adjacent surrounding tissue following an in vivo surgical procedure on the post-surgical site, the implant having a pre-implant configuration, which is defined as a configuration of the implant immediately before the implant is formed between the post-surgical site and the adjacent surrounding tissue, the implant comprising: a substantially planar membrane of resorbable polymer base material having a first substantially-smooth side and a second substantially-Smooth side, the substantially planar membrane of resorbable polymer base material comprising a layer of resorbable polymer base material between the first substantially-smooth side and the second substantially-smooth side, the layer of resorbable polymer base material having a substantially uniform composition; wherein a thickness of the layer of resorbable polymer base material, measured between the first substantially-smooth side and the second substantially-smooth side, is between about 10 microns and about 300 microns; wherein the layer of resorbable polymer base material is non-porous; and wherein the substantially planar membrane of resorbable polymer base material is sealed in a sterile packaging.
 15. The resorbable scar-tissue reduction micro-membrane set forth in claim 14, wherein the membrane comprises a substantially planar membrane of resorbable polymer base material having a first substantially-smooth side and the second substantially-smooth side, the substantially planar membrane of resorbable polymer base material comprising a single layer of resorbable polymer base material between the first substantially-smooth side and the second substantially-smooth side, the single layer of resorbable polymer base material having a substantially uniform composition. 